Association of cyclic AMP with markedly increased proliferation and reduced epidermal cell differentiation in psoriatic lesions is forwarded by numerous clinical reports that drugs which exacerbate psoriasis, such as propranolol, may do so by preventing cAMP accumulation. Adenylate cyclase (AC) of epidermal keratinocytes is most sensitive to Beta-adrenergic stimuli. And yet, psoriatic lesion tissue has decreased AC activity in response to isoproternol. Uninvolved skin of psoriatic subjects shows morphologic and metabolic abnormalities intermediate in value or similar to those in plaque areas. Therefore, we suggest that genetic differences in Beta-adrenergic sensitive-AC between epidermal tissue from psoriatic patients and normal subjects without psoriasis may be important in regulation of keratinocyte growth and maturation. I propose to quantify Beta-adrenergic receptors using radioligan binding assay procedures in particulate preparations of keratinocytes from psoriatic uninvolved and involved skin and normal skin, and further, to quantify receptors in intact keratinocytes in vitro derived from these tissues. I will also quantify receptors, assay the activity of AC after 3H-adenine prelabelling and agonist stimulation, and determine basal cAMP levels by radioimmunoassay of normal and psoriatic keratinocytes in vitro through proliferation and maturation phases. I will determine how pharmacologic manipulation of the Beta-adrenergic receptor with the agonist, isoproterenol, and the antagonist, propranolol, affect keratinocyte growth and associate these with changes in AC activity and basal cAMP levels. These studies will show whether 1) decreased numbers of Beta-adrenergic receptor sites might be responsible for decreased sensitivity of psoriatic epidermal tissue to catecholamine stimulation, 2) normal and psoriatic keratinocytes retain receptor numbers in vitro and how they may vary in quantity and sensitivity throughoutr proliferation and maturation, 3) basal cAMP and AC activity changes are associated with possible changes in Beta-adrenergic receptor sites in particulate preparations with those in intact keratinocytes grown in culture.